Bipolar Disorder

In addition to specific depressive or manic symptoms, more general symptoms also occur during the prodrome of both bipolar disorder type I and bipolar disorder type II, according to a report in the Journal of Affective Disorders.

For example, patients with both bipolar disorders frequently reported mood lability and disturbed diurnal rhythm during the months leading up to their first depressive or manic episode, said Dr. Eike Zeschel of Ruhr University, Bochum (Germany), and associates.

Even though most patients with bipolar disorder report having prodromal symptoms and signs, thus far those reported in the literature "appear neither sufficiently characteristic nor specific to allow the construction of empirically derived assessment instruments and symptom thresholds, or to suggest precise guidelines for the management of prodromal illness manifestations."

To further characterize the prodrome of bipolar disorder, Dr. Zeschel and colleagues performed structured interviews, which included administering the Bipolar Prodrome Symptom Scale–Retrospective and the Semi-Structured Interview for Mood Swings, with 42 bipolar participants who were treated at three university hospitals in Germany. They assessed 39 symptoms and signs that emerged or worsened before the first manic or depressive episode.

The mean age of these study subjects was 35 years, and 25 (approximately 60%) of them were women. A total of 27 patients had bipolar disorder type I and 15 had bipolar disorder type II.

The mean age at illness onset was 30 years (range, 18-58 years). The mean interval between the initial diagnosis of bipolar disorder and the study interview was 5-6 years. This means that all the study subjects were recalling experiences from several years earlier when responding to questions about their prodromal symptoms, the researchers noted.

All but one patient were taking psychotropic medication at the time of the interview. In addition, 9 patients had comorbid psychiatric problems such as substance use disorder or personality disorder, and 16 had physical comorbidities such as hypertension and thyroid dysfunction.

Overall, every patient with type I bipolar disorder and all but one patient with type II reported having at least one prodromal symptom just prior to their first episode.

The predepressive prodrome lasted significantly longer (4.1 months) than did the premanic prodrome (1.3 months). However, the frequency and severity of symptoms were similar between the two types of bipolar disorder.

The most frequently reported prodromal symptoms leading up to the first depressive episode were depressed mood, reduced vitality, physical exhaustion, tiredness, and social isolation. In contrast, the most frequently reported prodromal symptoms leading up to the first manic episode were feeling extremely energetic, physical agitation, talkativeness, racing thoughts, and low requirement for sleep.

However, general symptoms such as labile mood and disrupted sleep patterns also occurred frequently in both groups of patients. These "might be indicators for early recognition of bipolar disorder," Dr. Zeschel and associates said (J. Affect. Disord. 2013;151:551-60).

The first prodromal symptoms to appear in both patient groups were irritability, impatience, social isolation, weight gain, tiredness, and suspiciousness.

These findings highlight "the necessity to inquire about the patients’ entire psychopathological symptom ‘package’ and not only about specific affective symptoms when suspecting that they may be developing bipolar disorder," they said.

In general, prodromal symptoms showed "a progressive, accelerating course toward a full-blown mood episode." Symptoms "became more prevalent and more specific to the respective affective phase the closer the patients got to their mood episode," the investigators added.

Psychosis-like symptoms occurred significantly more often during a depressive than during a manic prodrome.

Dr. Zeschel and associates cited limitations. First, patients with both bipolar I and bipolar II were included in the study to get a larger sample size. Future studies are needed to focus on the separate subtypes of bipolar, they suggested. In addition, prodromal frequency and patterns might have been underreported "based on the assumption that patients are more likely to forget, minimize, or underreport symptoms," they wrote.

Nevertheless, these findings "support current approaches of early recognition programs for [bipolar disorder]," Dr. Zeschel and associates said.

More retrospective studies with larger patient populations would further clarify prodromal symptoms, and prospective studies "will be crucial to develop targeted early identification and intervention programs," they said.

Dr. Zeschel reported no conflicts of interest; Dr. Zeschel’s associates reported numerous ties to industry sources.

In addition to specific depressive or manic symptoms, more general symptoms also occur during the prodrome of both bipolar disorder type I and bipolar disorder type II, according to a report in the Journal of Affective Disorders.

For example, patients with both bipolar disorders frequently reported mood lability and disturbed diurnal rhythm during the months leading up to their first depressive or manic episode, said Dr. Eike Zeschel of Ruhr University, Bochum (Germany), and associates.

Even though most patients with bipolar disorder report having prodromal symptoms and signs, thus far those reported in the literature "appear neither sufficiently characteristic nor specific to allow the construction of empirically derived assessment instruments and symptom thresholds, or to suggest precise guidelines for the management of prodromal illness manifestations."

To further characterize the prodrome of bipolar disorder, Dr. Zeschel and colleagues performed structured interviews, which included administering the Bipolar Prodrome Symptom Scale–Retrospective and the Semi-Structured Interview for Mood Swings, with 42 bipolar participants who were treated at three university hospitals in Germany. They assessed 39 symptoms and signs that emerged or worsened before the first manic or depressive episode.

The mean age of these study subjects was 35 years, and 25 (approximately 60%) of them were women. A total of 27 patients had bipolar disorder type I and 15 had bipolar disorder type II.

The mean age at illness onset was 30 years (range, 18-58 years). The mean interval between the initial diagnosis of bipolar disorder and the study interview was 5-6 years. This means that all the study subjects were recalling experiences from several years earlier when responding to questions about their prodromal symptoms, the researchers noted.

All but one patient were taking psychotropic medication at the time of the interview. In addition, 9 patients had comorbid psychiatric problems such as substance use disorder or personality disorder, and 16 had physical comorbidities such as hypertension and thyroid dysfunction.

Overall, every patient with type I bipolar disorder and all but one patient with type II reported having at least one prodromal symptom just prior to their first episode.

The predepressive prodrome lasted significantly longer (4.1 months) than did the premanic prodrome (1.3 months). However, the frequency and severity of symptoms were similar between the two types of bipolar disorder.

The most frequently reported prodromal symptoms leading up to the first depressive episode were depressed mood, reduced vitality, physical exhaustion, tiredness, and social isolation. In contrast, the most frequently reported prodromal symptoms leading up to the first manic episode were feeling extremely energetic, physical agitation, talkativeness, racing thoughts, and low requirement for sleep.

However, general symptoms such as labile mood and disrupted sleep patterns also occurred frequently in both groups of patients. These "might be indicators for early recognition of bipolar disorder," Dr. Zeschel and associates said (J. Affect. Disord. 2013;151:551-60).

The first prodromal symptoms to appear in both patient groups were irritability, impatience, social isolation, weight gain, tiredness, and suspiciousness.

These findings highlight "the necessity to inquire about the patients’ entire psychopathological symptom ‘package’ and not only about specific affective symptoms when suspecting that they may be developing bipolar disorder," they said.

In general, prodromal symptoms showed "a progressive, accelerating course toward a full-blown mood episode." Symptoms "became more prevalent and more specific to the respective affective phase the closer the patients got to their mood episode," the investigators added.

Psychosis-like symptoms occurred significantly more often during a depressive than during a manic prodrome.

Dr. Zeschel and associates cited limitations. First, patients with both bipolar I and bipolar II were included in the study to get a larger sample size. Future studies are needed to focus on the separate subtypes of bipolar, they suggested. In addition, prodromal frequency and patterns might have been underreported "based on the assumption that patients are more likely to forget, minimize, or underreport symptoms," they wrote.

Nevertheless, these findings "support current approaches of early recognition programs for [bipolar disorder]," Dr. Zeschel and associates said.

More retrospective studies with larger patient populations would further clarify prodromal symptoms, and prospective studies "will be crucial to develop targeted early identification and intervention programs," they said.

Dr. Zeschel reported no conflicts of interest; Dr. Zeschel’s associates reported numerous ties to industry sources.

In addition to specific depressive or manic symptoms, more general symptoms also occur during the prodrome of both bipolar disorder type I and bipolar disorder type II, according to a report in the Journal of Affective Disorders.

For example, patients with both bipolar disorders frequently reported mood lability and disturbed diurnal rhythm during the months leading up to their first depressive or manic episode, said Dr. Eike Zeschel of Ruhr University, Bochum (Germany), and associates.

Even though most patients with bipolar disorder report having prodromal symptoms and signs, thus far those reported in the literature "appear neither sufficiently characteristic nor specific to allow the construction of empirically derived assessment instruments and symptom thresholds, or to suggest precise guidelines for the management of prodromal illness manifestations."

To further characterize the prodrome of bipolar disorder, Dr. Zeschel and colleagues performed structured interviews, which included administering the Bipolar Prodrome Symptom Scale–Retrospective and the Semi-Structured Interview for Mood Swings, with 42 bipolar participants who were treated at three university hospitals in Germany. They assessed 39 symptoms and signs that emerged or worsened before the first manic or depressive episode.

The mean age of these study subjects was 35 years, and 25 (approximately 60%) of them were women. A total of 27 patients had bipolar disorder type I and 15 had bipolar disorder type II.

The mean age at illness onset was 30 years (range, 18-58 years). The mean interval between the initial diagnosis of bipolar disorder and the study interview was 5-6 years. This means that all the study subjects were recalling experiences from several years earlier when responding to questions about their prodromal symptoms, the researchers noted.

All but one patient were taking psychotropic medication at the time of the interview. In addition, 9 patients had comorbid psychiatric problems such as substance use disorder or personality disorder, and 16 had physical comorbidities such as hypertension and thyroid dysfunction.

Overall, every patient with type I bipolar disorder and all but one patient with type II reported having at least one prodromal symptom just prior to their first episode.

The predepressive prodrome lasted significantly longer (4.1 months) than did the premanic prodrome (1.3 months). However, the frequency and severity of symptoms were similar between the two types of bipolar disorder.

The most frequently reported prodromal symptoms leading up to the first depressive episode were depressed mood, reduced vitality, physical exhaustion, tiredness, and social isolation. In contrast, the most frequently reported prodromal symptoms leading up to the first manic episode were feeling extremely energetic, physical agitation, talkativeness, racing thoughts, and low requirement for sleep.

However, general symptoms such as labile mood and disrupted sleep patterns also occurred frequently in both groups of patients. These "might be indicators for early recognition of bipolar disorder," Dr. Zeschel and associates said (J. Affect. Disord. 2013;151:551-60).

The first prodromal symptoms to appear in both patient groups were irritability, impatience, social isolation, weight gain, tiredness, and suspiciousness.

These findings highlight "the necessity to inquire about the patients’ entire psychopathological symptom ‘package’ and not only about specific affective symptoms when suspecting that they may be developing bipolar disorder," they said.

In general, prodromal symptoms showed "a progressive, accelerating course toward a full-blown mood episode." Symptoms "became more prevalent and more specific to the respective affective phase the closer the patients got to their mood episode," the investigators added.

Psychosis-like symptoms occurred significantly more often during a depressive than during a manic prodrome.

Dr. Zeschel and associates cited limitations. First, patients with both bipolar I and bipolar II were included in the study to get a larger sample size. Future studies are needed to focus on the separate subtypes of bipolar, they suggested. In addition, prodromal frequency and patterns might have been underreported "based on the assumption that patients are more likely to forget, minimize, or underreport symptoms," they wrote.

Nevertheless, these findings "support current approaches of early recognition programs for [bipolar disorder]," Dr. Zeschel and associates said.

More retrospective studies with larger patient populations would further clarify prodromal symptoms, and prospective studies "will be crucial to develop targeted early identification and intervention programs," they said.

Dr. Zeschel reported no conflicts of interest; Dr. Zeschel’s associates reported numerous ties to industry sources.

Thirty-two patients with bipolar disorder or major depressive disorder in remission showed similarly abnormal neural responses on functional brain imaging when presented with negative emotional stimuli, according to a report in NeuroImage.

Patients with bipolar disorder, however, showed different responses from those with major depressive disorder (MDD) when presented with positive emotional stimuli, reported Dr. Toshio Matsubara of the division of neuropsychiatry, Yamaguchi (Japan) University, and his associates.

"These findings indicate that bipolar disorder and major depressive disorder may have different neural circuits for emotional processing," compared with no mood disorder. They also suggest that abnormal neural responses might be a trait characteristic of both bipolar and major depressive disorder, the investigators said.

Dr. Matsubara and his colleagues used a noninvasive technique, functional near-infrared spectroscopy (fNIRS), to assess neural activity near the brain’s surface while study subjects were engaged in a cognitive task. The task was a Stroop test in which subjects had to read a word flashed on a video screen and identify the color of the typeface but ignore the emotional meaning of the word.

The displayed words were categorized as having happy, sad, threat, or neutral emotional impact and were shown in red, green, blue, or yellow typeface against a black background. Examples of happy words were "kindness" and "health," of sad words were "retirement" and "heartbreak," of threat words were "war" and "violence," and of neutral words were "name" and "iron."

The participants were 16 patients with bipolar disorder in remission (mean age, 44 years), 16 with MDD in remission (mean age, 45 years), and 20 healthy control subjects (mean age, 41 years). The control subjects were matched to case subjects for age, sex, handedness, and years of education.

In contrast to healthy control subjects, those with bipolar disorder or MDD showed hyperactivation of the prefrontal region during the threat stimuli. For happy words, patients with MDD showed prefrontal hyperactivation, but those with bipolar disorder showed prefrontal hypoactivation, Dr. Matsubara and his colleagues reported.

There were no significant differences among the three study groups in activity patterns during the sad or neutral stimuli, the investigators said (Neuroimage 2014;85:489-97).

This study was limited in that the small sample size likely restricted its statistical power. In addition, all of the participants with mood disorders were taking medications during testing, which might have blunted or otherwise altered their brain activity.

Still, Dr. Matsubara and his colleagues said that they hope their findings "may help to elucidate the different pathophysiologies underlying these two diseases."

One of Dr. Matsubara’s associates reported ties to numerous industry sources.

Thirty-two patients with bipolar disorder or major depressive disorder in remission showed similarly abnormal neural responses on functional brain imaging when presented with negative emotional stimuli, according to a report in NeuroImage.

Patients with bipolar disorder, however, showed different responses from those with major depressive disorder (MDD) when presented with positive emotional stimuli, reported Dr. Toshio Matsubara of the division of neuropsychiatry, Yamaguchi (Japan) University, and his associates.

"These findings indicate that bipolar disorder and major depressive disorder may have different neural circuits for emotional processing," compared with no mood disorder. They also suggest that abnormal neural responses might be a trait characteristic of both bipolar and major depressive disorder, the investigators said.

Dr. Matsubara and his colleagues used a noninvasive technique, functional near-infrared spectroscopy (fNIRS), to assess neural activity near the brain’s surface while study subjects were engaged in a cognitive task. The task was a Stroop test in which subjects had to read a word flashed on a video screen and identify the color of the typeface but ignore the emotional meaning of the word.

The displayed words were categorized as having happy, sad, threat, or neutral emotional impact and were shown in red, green, blue, or yellow typeface against a black background. Examples of happy words were "kindness" and "health," of sad words were "retirement" and "heartbreak," of threat words were "war" and "violence," and of neutral words were "name" and "iron."

The participants were 16 patients with bipolar disorder in remission (mean age, 44 years), 16 with MDD in remission (mean age, 45 years), and 20 healthy control subjects (mean age, 41 years). The control subjects were matched to case subjects for age, sex, handedness, and years of education.

In contrast to healthy control subjects, those with bipolar disorder or MDD showed hyperactivation of the prefrontal region during the threat stimuli. For happy words, patients with MDD showed prefrontal hyperactivation, but those with bipolar disorder showed prefrontal hypoactivation, Dr. Matsubara and his colleagues reported.

There were no significant differences among the three study groups in activity patterns during the sad or neutral stimuli, the investigators said (Neuroimage 2014;85:489-97).

This study was limited in that the small sample size likely restricted its statistical power. In addition, all of the participants with mood disorders were taking medications during testing, which might have blunted or otherwise altered their brain activity.

Still, Dr. Matsubara and his colleagues said that they hope their findings "may help to elucidate the different pathophysiologies underlying these two diseases."

One of Dr. Matsubara’s associates reported ties to numerous industry sources.

Thirty-two patients with bipolar disorder or major depressive disorder in remission showed similarly abnormal neural responses on functional brain imaging when presented with negative emotional stimuli, according to a report in NeuroImage.

Patients with bipolar disorder, however, showed different responses from those with major depressive disorder (MDD) when presented with positive emotional stimuli, reported Dr. Toshio Matsubara of the division of neuropsychiatry, Yamaguchi (Japan) University, and his associates.

"These findings indicate that bipolar disorder and major depressive disorder may have different neural circuits for emotional processing," compared with no mood disorder. They also suggest that abnormal neural responses might be a trait characteristic of both bipolar and major depressive disorder, the investigators said.

Dr. Matsubara and his colleagues used a noninvasive technique, functional near-infrared spectroscopy (fNIRS), to assess neural activity near the brain’s surface while study subjects were engaged in a cognitive task. The task was a Stroop test in which subjects had to read a word flashed on a video screen and identify the color of the typeface but ignore the emotional meaning of the word.

The displayed words were categorized as having happy, sad, threat, or neutral emotional impact and were shown in red, green, blue, or yellow typeface against a black background. Examples of happy words were "kindness" and "health," of sad words were "retirement" and "heartbreak," of threat words were "war" and "violence," and of neutral words were "name" and "iron."

The participants were 16 patients with bipolar disorder in remission (mean age, 44 years), 16 with MDD in remission (mean age, 45 years), and 20 healthy control subjects (mean age, 41 years). The control subjects were matched to case subjects for age, sex, handedness, and years of education.

In contrast to healthy control subjects, those with bipolar disorder or MDD showed hyperactivation of the prefrontal region during the threat stimuli. For happy words, patients with MDD showed prefrontal hyperactivation, but those with bipolar disorder showed prefrontal hypoactivation, Dr. Matsubara and his colleagues reported.

There were no significant differences among the three study groups in activity patterns during the sad or neutral stimuli, the investigators said (Neuroimage 2014;85:489-97).

This study was limited in that the small sample size likely restricted its statistical power. In addition, all of the participants with mood disorders were taking medications during testing, which might have blunted or otherwise altered their brain activity.

Still, Dr. Matsubara and his colleagues said that they hope their findings "may help to elucidate the different pathophysiologies underlying these two diseases."

One of Dr. Matsubara’s associates reported ties to numerous industry sources.

Combining a mood stabilizer with a second-generation atypical antipsychotic is more effective than monotherapy for preventing relapses in bipolar disorder, a review in the Journal of Affective Disorders shows.

However, combined treatments carry a greater risk of adverse effects, including potentially lethal conditions, especially when they are used long-term. As a result, clinicians should be cautious about prescribing these combination regimens. Such regiments should be reserved for patients who do not achieve clinical stability with monotherapy and do not have significant medical comorbidities, said Dr. Massimiliano Buoli of the University of Milan and his associates.

The investigators reviewed the literature on combined mood stabilizer plus antipsychotic therapy for the maintenance treatment of bipolar disorder, focusing on 19 studies published between 1980 and 2013.

"With some exceptions," they found combination therapy more effective than monotherapy at preventing relapses. But the paucity of high-quality data means that "it is probably too early to have a definitive opinion about the best atypical antipsychotic to combine with mood stabilizers," the researchers wrote (J. Affect. Disord. 2014;152:12-18).

First-generation antipsychotics should not be used in this way, however, as they raise the risk of motor adverse effects excessively.

Among atypical antipsychotics, quetiapine has accumulated the most evidence regarding efficacy. Ziprasidone and long-acting risperidone also boast low rates of relapse, compared with other agents.

Case reports indicate that all combined therapies with the exception of ziprasidone raise the risk of potentially fatal adverse events, including encephalopathy, Stevens-Johnson syndrome, neutropenia, and neuroleptic malignant syndrome. Olanzapine, risperidone, and quetiapine are associated with a higher risk of weight gain, and aripiprazole and ziprasidone have been linked to a higher risk of extrapyramidal side effects.

Dr. Buoli reported that he is a consultant for Roche, and his associate Dr. A. Carlo Altamura reported ties to Roche, Merck, and other companies.

Combining a mood stabilizer with a second-generation atypical antipsychotic is more effective than monotherapy for preventing relapses in bipolar disorder, a review in the Journal of Affective Disorders shows.

However, combined treatments carry a greater risk of adverse effects, including potentially lethal conditions, especially when they are used long-term. As a result, clinicians should be cautious about prescribing these combination regimens. Such regiments should be reserved for patients who do not achieve clinical stability with monotherapy and do not have significant medical comorbidities, said Dr. Massimiliano Buoli of the University of Milan and his associates.

The investigators reviewed the literature on combined mood stabilizer plus antipsychotic therapy for the maintenance treatment of bipolar disorder, focusing on 19 studies published between 1980 and 2013.

"With some exceptions," they found combination therapy more effective than monotherapy at preventing relapses. But the paucity of high-quality data means that "it is probably too early to have a definitive opinion about the best atypical antipsychotic to combine with mood stabilizers," the researchers wrote (J. Affect. Disord. 2014;152:12-18).

First-generation antipsychotics should not be used in this way, however, as they raise the risk of motor adverse effects excessively.

Among atypical antipsychotics, quetiapine has accumulated the most evidence regarding efficacy. Ziprasidone and long-acting risperidone also boast low rates of relapse, compared with other agents.

Case reports indicate that all combined therapies with the exception of ziprasidone raise the risk of potentially fatal adverse events, including encephalopathy, Stevens-Johnson syndrome, neutropenia, and neuroleptic malignant syndrome. Olanzapine, risperidone, and quetiapine are associated with a higher risk of weight gain, and aripiprazole and ziprasidone have been linked to a higher risk of extrapyramidal side effects.

Dr. Buoli reported that he is a consultant for Roche, and his associate Dr. A. Carlo Altamura reported ties to Roche, Merck, and other companies.

Combining a mood stabilizer with a second-generation atypical antipsychotic is more effective than monotherapy for preventing relapses in bipolar disorder, a review in the Journal of Affective Disorders shows.

However, combined treatments carry a greater risk of adverse effects, including potentially lethal conditions, especially when they are used long-term. As a result, clinicians should be cautious about prescribing these combination regimens. Such regiments should be reserved for patients who do not achieve clinical stability with monotherapy and do not have significant medical comorbidities, said Dr. Massimiliano Buoli of the University of Milan and his associates.

The investigators reviewed the literature on combined mood stabilizer plus antipsychotic therapy for the maintenance treatment of bipolar disorder, focusing on 19 studies published between 1980 and 2013.

"With some exceptions," they found combination therapy more effective than monotherapy at preventing relapses. But the paucity of high-quality data means that "it is probably too early to have a definitive opinion about the best atypical antipsychotic to combine with mood stabilizers," the researchers wrote (J. Affect. Disord. 2014;152:12-18).

First-generation antipsychotics should not be used in this way, however, as they raise the risk of motor adverse effects excessively.

Among atypical antipsychotics, quetiapine has accumulated the most evidence regarding efficacy. Ziprasidone and long-acting risperidone also boast low rates of relapse, compared with other agents.

Case reports indicate that all combined therapies with the exception of ziprasidone raise the risk of potentially fatal adverse events, including encephalopathy, Stevens-Johnson syndrome, neutropenia, and neuroleptic malignant syndrome. Olanzapine, risperidone, and quetiapine are associated with a higher risk of weight gain, and aripiprazole and ziprasidone have been linked to a higher risk of extrapyramidal side effects.

Dr. Buoli reported that he is a consultant for Roche, and his associate Dr. A. Carlo Altamura reported ties to Roche, Merck, and other companies.

BARCELONA – The greatest risk that patients with schizophrenia will develop extrapyramidal symptoms while on treatment with a second-generation antipsychotic drug comes during the first few weeks of treatment, and then substantially resolves during the rest of the first year on treatment, according to findings from a multicenter European trial with 498 patients.

In addition, the risk level varies from drug to drug, and some extrapyramidal symptoms are rare, with no treatment-related episodes of dystonia and dyskinesia, including tardive dyskinesia, during the year on treatment, Dr. Janusz K. Rybakowski said at the annual congress of the European College of Neuropsychopharmacology.

"Generally, it can be stated that extrapyramidal symptoms are not much of a problem for patients taking second-generation antipsychotic drugs except for the problem of akathisia with ziprasidone treatment, which should be taken into account" when considering which drug to prescribe, said Dr. Rybakowski, professor and head of adult psychiatry at Poznañ (Poland) University.

In the study, 24% of newly diagnosed schizophrenia patients who received ziprasidone as their initial treatment developed akathisia by 1 month after starting treatment. However, among patients who remained in the study and on ziprasidone treatment for 1 year, the prevalence of akathisia fell to less than 9%, he reported. The analysis also documented the rates at which patients developed parkinsonian symptoms.

Second-generation antipsychotics "have to be looked at for their risk-benefit profile," commented Dr. W. Wolfgang Fleischhacker, professor and director of psychiatry at the Medical University of Innsbruck, Austria, and a EUFEST (European First Episode of Schizophrenia Trial) coinvestigator. "Some of these drugs have problems, but they are also effective. Some may have problems causing metabolic syndrome but not extrapyramidal symptoms, and vise versa. And we lack good predictors" for which patients will develop significant adverse effects on treatment. "Even if olanzapine is the biggest offender with regard to metabolic disturbances, probably only 40% of patients are affected. So we can’t judge these drugs generally; we need to closely monitor patients" to see which ones actually develop a significant adverse effect on treatment, Dr. Fleischhacker said.

Dr. Rybakowski and his associates used data collected in EUFEST, which enrolled 498 patients at 50 centers in Europe and in Israel (Lancet 2008;371:1085-97). The investigators randomized patients to treatment with olanzapine, quetiapine, amisulpride, ziprasidone, or to the first-generation antipsychotic haloperidol.

After 1 month, the incidence of parkinsonian symptoms ranged from 4% among those on olanzapine to 13% of those on ziprasidone (and 26% for those on haloperidol). But by 12 months, the rate had dropped to zero among patients on olanzapine and also dropped among all other patients. At 1 year, the highest rate, 9%, was among patients on haloperidol. After 1 month, the incidence of akathisia ranged from 3% among those on olanzapine to 24% for those on ziprasidone (and 21% for patients on haloperidol); after 12 months, the rate fell to zero in patients on olanzapine or amisulpride and was highest, at 7%, among patients on quetiapine.

Although no patients on any second-generation drug developed new symptoms of dystonia or dyskinesia, a few on haloperidol developed dyskinesia.

The percent of patients receiving an anticholinergic drug at 1 month to treat their extrapyramidal symptoms ranged from 13% of those on ziprasidone, 10% on amisulpride, 3% on olanzapine, 2% on quetiapine, and 24% on haloperidol. After 12 months, the rate of anticholinergic drug use fell to a high of 11% on haloperidol and 6% for amisulpride. Patients on all the other second-generation antipsychotics had lower rates of anticholinergic drug use.

EUFEST was sponsored by AstraZeneca, Sanofi-Aventis, and Pfizer. Dr. Rybakowski said he has been a consultant to Adamed, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Sanofi-Aventis, and Servier. Dr. Fleischhacker has received honoraria as a speaker or consultant to Bristol-Myers Squibb, Janssen, Lundbeck, MedAvante, Merck, Otsuka, Pfizer, and Roche.

[email protected]

On Twitter @mitchelzoler

BARCELONA – The greatest risk that patients with schizophrenia will develop extrapyramidal symptoms while on treatment with a second-generation antipsychotic drug comes during the first few weeks of treatment, and then substantially resolves during the rest of the first year on treatment, according to findings from a multicenter European trial with 498 patients.

In addition, the risk level varies from drug to drug, and some extrapyramidal symptoms are rare, with no treatment-related episodes of dystonia and dyskinesia, including tardive dyskinesia, during the year on treatment, Dr. Janusz K. Rybakowski said at the annual congress of the European College of Neuropsychopharmacology.

"Generally, it can be stated that extrapyramidal symptoms are not much of a problem for patients taking second-generation antipsychotic drugs except for the problem of akathisia with ziprasidone treatment, which should be taken into account" when considering which drug to prescribe, said Dr. Rybakowski, professor and head of adult psychiatry at Poznañ (Poland) University.

In the study, 24% of newly diagnosed schizophrenia patients who received ziprasidone as their initial treatment developed akathisia by 1 month after starting treatment. However, among patients who remained in the study and on ziprasidone treatment for 1 year, the prevalence of akathisia fell to less than 9%, he reported. The analysis also documented the rates at which patients developed parkinsonian symptoms.

Second-generation antipsychotics "have to be looked at for their risk-benefit profile," commented Dr. W. Wolfgang Fleischhacker, professor and director of psychiatry at the Medical University of Innsbruck, Austria, and a EUFEST (European First Episode of Schizophrenia Trial) coinvestigator. "Some of these drugs have problems, but they are also effective. Some may have problems causing metabolic syndrome but not extrapyramidal symptoms, and vise versa. And we lack good predictors" for which patients will develop significant adverse effects on treatment. "Even if olanzapine is the biggest offender with regard to metabolic disturbances, probably only 40% of patients are affected. So we can’t judge these drugs generally; we need to closely monitor patients" to see which ones actually develop a significant adverse effect on treatment, Dr. Fleischhacker said.

Dr. Rybakowski and his associates used data collected in EUFEST, which enrolled 498 patients at 50 centers in Europe and in Israel (Lancet 2008;371:1085-97). The investigators randomized patients to treatment with olanzapine, quetiapine, amisulpride, ziprasidone, or to the first-generation antipsychotic haloperidol.

After 1 month, the incidence of parkinsonian symptoms ranged from 4% among those on olanzapine to 13% of those on ziprasidone (and 26% for those on haloperidol). But by 12 months, the rate had dropped to zero among patients on olanzapine and also dropped among all other patients. At 1 year, the highest rate, 9%, was among patients on haloperidol. After 1 month, the incidence of akathisia ranged from 3% among those on olanzapine to 24% for those on ziprasidone (and 21% for patients on haloperidol); after 12 months, the rate fell to zero in patients on olanzapine or amisulpride and was highest, at 7%, among patients on quetiapine.

Although no patients on any second-generation drug developed new symptoms of dystonia or dyskinesia, a few on haloperidol developed dyskinesia.

The percent of patients receiving an anticholinergic drug at 1 month to treat their extrapyramidal symptoms ranged from 13% of those on ziprasidone, 10% on amisulpride, 3% on olanzapine, 2% on quetiapine, and 24% on haloperidol. After 12 months, the rate of anticholinergic drug use fell to a high of 11% on haloperidol and 6% for amisulpride. Patients on all the other second-generation antipsychotics had lower rates of anticholinergic drug use.

EUFEST was sponsored by AstraZeneca, Sanofi-Aventis, and Pfizer. Dr. Rybakowski said he has been a consultant to Adamed, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Sanofi-Aventis, and Servier. Dr. Fleischhacker has received honoraria as a speaker or consultant to Bristol-Myers Squibb, Janssen, Lundbeck, MedAvante, Merck, Otsuka, Pfizer, and Roche.

[email protected]

On Twitter @mitchelzoler

BARCELONA – The greatest risk that patients with schizophrenia will develop extrapyramidal symptoms while on treatment with a second-generation antipsychotic drug comes during the first few weeks of treatment, and then substantially resolves during the rest of the first year on treatment, according to findings from a multicenter European trial with 498 patients.

In addition, the risk level varies from drug to drug, and some extrapyramidal symptoms are rare, with no treatment-related episodes of dystonia and dyskinesia, including tardive dyskinesia, during the year on treatment, Dr. Janusz K. Rybakowski said at the annual congress of the European College of Neuropsychopharmacology.

"Generally, it can be stated that extrapyramidal symptoms are not much of a problem for patients taking second-generation antipsychotic drugs except for the problem of akathisia with ziprasidone treatment, which should be taken into account" when considering which drug to prescribe, said Dr. Rybakowski, professor and head of adult psychiatry at Poznañ (Poland) University.

In the study, 24% of newly diagnosed schizophrenia patients who received ziprasidone as their initial treatment developed akathisia by 1 month after starting treatment. However, among patients who remained in the study and on ziprasidone treatment for 1 year, the prevalence of akathisia fell to less than 9%, he reported. The analysis also documented the rates at which patients developed parkinsonian symptoms.

Second-generation antipsychotics "have to be looked at for their risk-benefit profile," commented Dr. W. Wolfgang Fleischhacker, professor and director of psychiatry at the Medical University of Innsbruck, Austria, and a EUFEST (European First Episode of Schizophrenia Trial) coinvestigator. "Some of these drugs have problems, but they are also effective. Some may have problems causing metabolic syndrome but not extrapyramidal symptoms, and vise versa. And we lack good predictors" for which patients will develop significant adverse effects on treatment. "Even if olanzapine is the biggest offender with regard to metabolic disturbances, probably only 40% of patients are affected. So we can’t judge these drugs generally; we need to closely monitor patients" to see which ones actually develop a significant adverse effect on treatment, Dr. Fleischhacker said.

Dr. Rybakowski and his associates used data collected in EUFEST, which enrolled 498 patients at 50 centers in Europe and in Israel (Lancet 2008;371:1085-97). The investigators randomized patients to treatment with olanzapine, quetiapine, amisulpride, ziprasidone, or to the first-generation antipsychotic haloperidol.

After 1 month, the incidence of parkinsonian symptoms ranged from 4% among those on olanzapine to 13% of those on ziprasidone (and 26% for those on haloperidol). But by 12 months, the rate had dropped to zero among patients on olanzapine and also dropped among all other patients. At 1 year, the highest rate, 9%, was among patients on haloperidol. After 1 month, the incidence of akathisia ranged from 3% among those on olanzapine to 24% for those on ziprasidone (and 21% for patients on haloperidol); after 12 months, the rate fell to zero in patients on olanzapine or amisulpride and was highest, at 7%, among patients on quetiapine.

Although no patients on any second-generation drug developed new symptoms of dystonia or dyskinesia, a few on haloperidol developed dyskinesia.

The percent of patients receiving an anticholinergic drug at 1 month to treat their extrapyramidal symptoms ranged from 13% of those on ziprasidone, 10% on amisulpride, 3% on olanzapine, 2% on quetiapine, and 24% on haloperidol. After 12 months, the rate of anticholinergic drug use fell to a high of 11% on haloperidol and 6% for amisulpride. Patients on all the other second-generation antipsychotics had lower rates of anticholinergic drug use.

EUFEST was sponsored by AstraZeneca, Sanofi-Aventis, and Pfizer. Dr. Rybakowski said he has been a consultant to Adamed, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Sanofi-Aventis, and Servier. Dr. Fleischhacker has received honoraria as a speaker or consultant to Bristol-Myers Squibb, Janssen, Lundbeck, MedAvante, Merck, Otsuka, Pfizer, and Roche.

[email protected]

On Twitter @mitchelzoler

ORLANDO – History of self-harm and suicidal ideation are two strong indicators that a teen with bipolar disorder might attempt suicide, according to an unpublished Canadian study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Identifying such clinical features is important as they can help with intervention and prevention of suicide among teens with bipolar disorder, the researchers wrote.

Previous studies have shown that adults with bipolar disorder (BD) are at a higher risk of completing suicide – as many as 25%-50% of them make at least one suicide attempt in their lifetime, and up to 20% complete the attempt.

Meanwhile, studies of pediatric patients have shown a lifetime suicide attempt rate of 20%-50%. Yet there is limited research on teens, Dr. Benjamin I. Goldstein of Sunnybrook Health Sciences Centre, Toronto, and his colleagues wrote in their poster.

A 2013 systemic review of suicidal ideation and suicide attempts by children and teenagers with bipolar disorder showed that the issue is underinvestigated. "Exploration of predictors and protective factors is imperative for the establishment of effective preventive and intervention strategies, which are urgently needed," researchers at Zucker Hillside Hospital, Glen Oaks, N.Y., wrote (Bipolar Disord. 2013;15:507-23).

Dr. Goldstein and his colleagues studied 72 teenagers aged 13-19 years who had bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified.

The 20% of patients who reported having attempted suicide were significantly more likely to be female and to have lower socioeconomic status, more self-harm behavior, suicide ideation, a lifetime history of conduct disorder, bulimia nervosa, lifetime lamotrigine use, and a family history of suicide attempts. That’s compared with teens who did not attempt a suicide.

The multivariate analyses showed that history of self-injurious behavior and family history of suicide attempts was strongly associated with suicide attempts. And when comparing the findings from previous studies and the current study, the researchers found that they all shared history of self-injurious behavior and suicidal ideation.

The analyses had limited power to detect small effect sizes, and "the cross-sectional methodology precludes conclusions regarding the directionality of the observed associations," Dr. Goldstein and his colleagues wrote.

They added that future studies should examine whether the characteristics found in the study can be incorporated in assessment and treatment of youth with bipolar disorder to help reduce the risk of suicide in this high-risk population.

Dr. Goldstein is a consultant for Bristol-Myers Squibb and has received honoraria from Purdue Pharma.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – History of self-harm and suicidal ideation are two strong indicators that a teen with bipolar disorder might attempt suicide, according to an unpublished Canadian study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Identifying such clinical features is important as they can help with intervention and prevention of suicide among teens with bipolar disorder, the researchers wrote.

Previous studies have shown that adults with bipolar disorder (BD) are at a higher risk of completing suicide – as many as 25%-50% of them make at least one suicide attempt in their lifetime, and up to 20% complete the attempt.

Meanwhile, studies of pediatric patients have shown a lifetime suicide attempt rate of 20%-50%. Yet there is limited research on teens, Dr. Benjamin I. Goldstein of Sunnybrook Health Sciences Centre, Toronto, and his colleagues wrote in their poster.

A 2013 systemic review of suicidal ideation and suicide attempts by children and teenagers with bipolar disorder showed that the issue is underinvestigated. "Exploration of predictors and protective factors is imperative for the establishment of effective preventive and intervention strategies, which are urgently needed," researchers at Zucker Hillside Hospital, Glen Oaks, N.Y., wrote (Bipolar Disord. 2013;15:507-23).

Dr. Goldstein and his colleagues studied 72 teenagers aged 13-19 years who had bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified.

The 20% of patients who reported having attempted suicide were significantly more likely to be female and to have lower socioeconomic status, more self-harm behavior, suicide ideation, a lifetime history of conduct disorder, bulimia nervosa, lifetime lamotrigine use, and a family history of suicide attempts. That’s compared with teens who did not attempt a suicide.

The multivariate analyses showed that history of self-injurious behavior and family history of suicide attempts was strongly associated with suicide attempts. And when comparing the findings from previous studies and the current study, the researchers found that they all shared history of self-injurious behavior and suicidal ideation.

The analyses had limited power to detect small effect sizes, and "the cross-sectional methodology precludes conclusions regarding the directionality of the observed associations," Dr. Goldstein and his colleagues wrote.

They added that future studies should examine whether the characteristics found in the study can be incorporated in assessment and treatment of youth with bipolar disorder to help reduce the risk of suicide in this high-risk population.

Dr. Goldstein is a consultant for Bristol-Myers Squibb and has received honoraria from Purdue Pharma.

[email protected]

On Twitter @NaseemSMiller

ORLANDO – History of self-harm and suicidal ideation are two strong indicators that a teen with bipolar disorder might attempt suicide, according to an unpublished Canadian study presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

Identifying such clinical features is important as they can help with intervention and prevention of suicide among teens with bipolar disorder, the researchers wrote.

Previous studies have shown that adults with bipolar disorder (BD) are at a higher risk of completing suicide – as many as 25%-50% of them make at least one suicide attempt in their lifetime, and up to 20% complete the attempt.

Meanwhile, studies of pediatric patients have shown a lifetime suicide attempt rate of 20%-50%. Yet there is limited research on teens, Dr. Benjamin I. Goldstein of Sunnybrook Health Sciences Centre, Toronto, and his colleagues wrote in their poster.

A 2013 systemic review of suicidal ideation and suicide attempts by children and teenagers with bipolar disorder showed that the issue is underinvestigated. "Exploration of predictors and protective factors is imperative for the establishment of effective preventive and intervention strategies, which are urgently needed," researchers at Zucker Hillside Hospital, Glen Oaks, N.Y., wrote (Bipolar Disord. 2013;15:507-23).

Dr. Goldstein and his colleagues studied 72 teenagers aged 13-19 years who had bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified.

The 20% of patients who reported having attempted suicide were significantly more likely to be female and to have lower socioeconomic status, more self-harm behavior, suicide ideation, a lifetime history of conduct disorder, bulimia nervosa, lifetime lamotrigine use, and a family history of suicide attempts. That’s compared with teens who did not attempt a suicide.

The multivariate analyses showed that history of self-injurious behavior and family history of suicide attempts was strongly associated with suicide attempts. And when comparing the findings from previous studies and the current study, the researchers found that they all shared history of self-injurious behavior and suicidal ideation.

The analyses had limited power to detect small effect sizes, and "the cross-sectional methodology precludes conclusions regarding the directionality of the observed associations," Dr. Goldstein and his colleagues wrote.

They added that future studies should examine whether the characteristics found in the study can be incorporated in assessment and treatment of youth with bipolar disorder to help reduce the risk of suicide in this high-risk population.

Dr. Goldstein is a consultant for Bristol-Myers Squibb and has received honoraria from Purdue Pharma.

[email protected]

On Twitter @NaseemSMiller

PHILADELPHIA – Former congressman Patrick Kennedy says that psychiatrists have a unique opportunity to advance their profession and assume a more active role in the health care system now that the Affordable Care Act is underway.

"With health care reform, we’re rewriting the rule book on what health care means," said Mr. Kennedy, at the American Psychiatric Association’s annual institute on psychiatric services. Mr. Kennedy was interviewed by APA President Jeffrey Lieberman.

Alicia Ault/IMNG Medical Media

"Now, mental health is going to be an essential health benefit," Mr. Kennedy added. That means psychiatrists need to step up and say what they think needs to be included and what should be reimbursed, he said.

"We need your thinking now. Giving it to us 5 years from now is going to be a lost cause," said Mr. Kennedy, a former Democratic House member from Rhode Island who has been very public about his struggles with bipolar disorder and substance abuse.

Mr. Kennedy urged psychiatrists to push for an end to what he called the "silos" between intellectual disabilities and mental health disorders, noting that many of the services required were similar.

Dr. Lieberman agreed, saying that "this artificial separation between intellectual disabilities, mental disorders, substance use, and addiction" should end, but that it was up to psychiatry to tell policy makers how best to do that.

He asked Mr. Kennedy his opinion of some of the key policy challenges for psychiatry, especially under the new health law.

For one, psychiatrists should focus more on adequately diagnosing patients from a medical standpoint – that is, assessing their coexisting conditions and helping to integrate medical and psychiatric care, Mr. Kennedy said. This will help generate bottom line savings for accountable care organizations and, in turn, validate the profession’s value, he said.

"You all have the key to treating cancer better," he said. "You all have the key to treating diabetes and cardiovascular disease better. And no one’s ever thought of calling you!"

As it stands in most of the health system, the rest of the medical profession does not have adequate training in psychiatry and does not know how to reach out to psychiatrists, he said. "Insurance companies ought to know that by paying for the kind of value added that you bring, they’ll get value added to their bottom lines," said Mr. Kennedy, adding that many chronic conditions are "driven by untreated mental illness."

He also reminded psychiatrists that they need to keep campaigning for parity between physical and mental health when it comes to coverage and reimbursement, even though it is the law. Everyone in the mental health field should band together to make sure parity becomes reality, he said.

Dr. Lieberman agreed, saying, "We have to demonstrate some leadership." He said that the APA could be the lead organization bringing others together.

"This is a moment in history where we have a chance to change the landscape," Dr. Lieberman said.

[email protected]

On Twitter @aliciaault

PHILADELPHIA – Former congressman Patrick Kennedy says that psychiatrists have a unique opportunity to advance their profession and assume a more active role in the health care system now that the Affordable Care Act is underway.

"With health care reform, we’re rewriting the rule book on what health care means," said Mr. Kennedy, at the American Psychiatric Association’s annual institute on psychiatric services. Mr. Kennedy was interviewed by APA President Jeffrey Lieberman.

Alicia Ault/IMNG Medical Media

"Now, mental health is going to be an essential health benefit," Mr. Kennedy added. That means psychiatrists need to step up and say what they think needs to be included and what should be reimbursed, he said.

"We need your thinking now. Giving it to us 5 years from now is going to be a lost cause," said Mr. Kennedy, a former Democratic House member from Rhode Island who has been very public about his struggles with bipolar disorder and substance abuse.

Mr. Kennedy urged psychiatrists to push for an end to what he called the "silos" between intellectual disabilities and mental health disorders, noting that many of the services required were similar.

Dr. Lieberman agreed, saying that "this artificial separation between intellectual disabilities, mental disorders, substance use, and addiction" should end, but that it was up to psychiatry to tell policy makers how best to do that.

He asked Mr. Kennedy his opinion of some of the key policy challenges for psychiatry, especially under the new health law.

For one, psychiatrists should focus more on adequately diagnosing patients from a medical standpoint – that is, assessing their coexisting conditions and helping to integrate medical and psychiatric care, Mr. Kennedy said. This will help generate bottom line savings for accountable care organizations and, in turn, validate the profession’s value, he said.

"You all have the key to treating cancer better," he said. "You all have the key to treating diabetes and cardiovascular disease better. And no one’s ever thought of calling you!"

As it stands in most of the health system, the rest of the medical profession does not have adequate training in psychiatry and does not know how to reach out to psychiatrists, he said. "Insurance companies ought to know that by paying for the kind of value added that you bring, they’ll get value added to their bottom lines," said Mr. Kennedy, adding that many chronic conditions are "driven by untreated mental illness."

He also reminded psychiatrists that they need to keep campaigning for parity between physical and mental health when it comes to coverage and reimbursement, even though it is the law. Everyone in the mental health field should band together to make sure parity becomes reality, he said.

Dr. Lieberman agreed, saying, "We have to demonstrate some leadership." He said that the APA could be the lead organization bringing others together.

"This is a moment in history where we have a chance to change the landscape," Dr. Lieberman said.

[email protected]

On Twitter @aliciaault

PHILADELPHIA – Former congressman Patrick Kennedy says that psychiatrists have a unique opportunity to advance their profession and assume a more active role in the health care system now that the Affordable Care Act is underway.

"With health care reform, we’re rewriting the rule book on what health care means," said Mr. Kennedy, at the American Psychiatric Association’s annual institute on psychiatric services. Mr. Kennedy was interviewed by APA President Jeffrey Lieberman.

Alicia Ault/IMNG Medical Media

"Now, mental health is going to be an essential health benefit," Mr. Kennedy added. That means psychiatrists need to step up and say what they think needs to be included and what should be reimbursed, he said.

"We need your thinking now. Giving it to us 5 years from now is going to be a lost cause," said Mr. Kennedy, a former Democratic House member from Rhode Island who has been very public about his struggles with bipolar disorder and substance abuse.

Mr. Kennedy urged psychiatrists to push for an end to what he called the "silos" between intellectual disabilities and mental health disorders, noting that many of the services required were similar.

Dr. Lieberman agreed, saying that "this artificial separation between intellectual disabilities, mental disorders, substance use, and addiction" should end, but that it was up to psychiatry to tell policy makers how best to do that.

He asked Mr. Kennedy his opinion of some of the key policy challenges for psychiatry, especially under the new health law.

For one, psychiatrists should focus more on adequately diagnosing patients from a medical standpoint – that is, assessing their coexisting conditions and helping to integrate medical and psychiatric care, Mr. Kennedy said. This will help generate bottom line savings for accountable care organizations and, in turn, validate the profession’s value, he said.

"You all have the key to treating cancer better," he said. "You all have the key to treating diabetes and cardiovascular disease better. And no one’s ever thought of calling you!"

As it stands in most of the health system, the rest of the medical profession does not have adequate training in psychiatry and does not know how to reach out to psychiatrists, he said. "Insurance companies ought to know that by paying for the kind of value added that you bring, they’ll get value added to their bottom lines," said Mr. Kennedy, adding that many chronic conditions are "driven by untreated mental illness."

He also reminded psychiatrists that they need to keep campaigning for parity between physical and mental health when it comes to coverage and reimbursement, even though it is the law. Everyone in the mental health field should band together to make sure parity becomes reality, he said.

Dr. Lieberman agreed, saying, "We have to demonstrate some leadership." He said that the APA could be the lead organization bringing others together.

"This is a moment in history where we have a chance to change the landscape," Dr. Lieberman said.

[email protected]

On Twitter @aliciaault

BARCELONA – Armodafinil, a drug with Food and Drug Administration approval to treat excessive sleepiness and narcolepsy, showed efficacy for improving concentration, energy, and appetite in a controlled study of nearly 400 patients with bipolar I depression.

"I think [armodafinil] is clinically useful because its efficacy appears complementary to the efficacy we see from other compounds," Dr. Joseph R. Calabrese said at the annual congress of the European College of Neuropsychopharmacology.

Mitchel L. Zoler/IMNG Medical Media

In addition to showing useful efficacy compared with placebo as adjunctive treatment, armodafinil also had a "very, very benign" adverse effect profile – its 6% dropout rate because of adverse effects was not statistically significant from the 4% rate in placebo patients.

Armodafinil is the R-enantiomer of modafinil, which means the two agents are essentially the same. "I think off-label use [of armodafinil] is okay, because there are a lot of [safety] data for modafinil," Dr. Calabrese said in an interview.

Armodafinil (Nuvigil) has FDA approval for treating shift-work disorder, narcolepsy, and treated obstructed sleep apnea. He foresees no push for formal labeling of armodafinil for bipolar I depression because three phase III trials were run and only one was positive for efficacy. The two trials that failed to prove efficacy fell short not because of a blunted drug effect but because of an unexpectedly high response in the placebo group. This design flaw in two of the three pivotal trials likely doomed any hope of getting armodafinil labeled for this indication, he said.

"There is a role for armodafinil. It is something to try for patients" who need help in the things it affects, said Dr. Calabrese, professor of psychiatry and head of the mood disorders program at Case Western Reserve University in Cleveland. "It has stimulant-like properties that can improve concentration" and can help patients who are on another drug causing sedation, he added.

The study he ran enrolled patients who had cycled into a new major depressive episode after treatment with antimanic drugs for at least 4 weeks. Most patients were on antimanic monotherapy during the study, about 10% were on two antimanic drugs, and two patients were on three drugs. The researchers randomized 198 patients to receive 150 mg of armodafinil daily and 199 to placebo. An additional 32 patients initially received 200 mg armodafinil daily, but that arm was discontinued because of adverse effects.

After 8 weeks, the study’s primary endpoint – change in average, total clinician-rated, 30-item Inventory of Depressive Symptomatology (IDS) score – showed a 21.7 point drop with armodafinil and a 17.9 point drop with placebo, a statistically significant difference. The incidence of responder patients, those with at least a 50% reduction from their baseline IDS score, was 46% in the armodafinil arm and 34% in the placebo arm, a statistically significant difference and indicating a number needed to treat of nine to achieve one additional response over placebo.

The results also showed that the improvements in IDS score focused on five of the score’s 30 individual items: panic and phobic symptoms, appetite, concentration and decision making, energy and fatigability, and leaden paralysis and physical energy. In contrast, armodafinil had no apparent effect on core symptoms of depression. Armodafinil also produced no worsening of anxiety, sleep, or switch rates, and no meaningful trends toward gain or loss of weight.

The study was sponsored by Teva, which markets armodafinil (Nuvigil). Dr. Calabrese said that he has been a consultant to and received research support from Teva and more than a dozen other drug companies.

[email protected]

On Twitter @mitchelzoler

BARCELONA – Armodafinil, a drug with Food and Drug Administration approval to treat excessive sleepiness and narcolepsy, showed efficacy for improving concentration, energy, and appetite in a controlled study of nearly 400 patients with bipolar I depression.

"I think [armodafinil] is clinically useful because its efficacy appears complementary to the efficacy we see from other compounds," Dr. Joseph R. Calabrese said at the annual congress of the European College of Neuropsychopharmacology.

Mitchel L. Zoler/IMNG Medical Media

In addition to showing useful efficacy compared with placebo as adjunctive treatment, armodafinil also had a "very, very benign" adverse effect profile – its 6% dropout rate because of adverse effects was not statistically significant from the 4% rate in placebo patients.

Armodafinil is the R-enantiomer of modafinil, which means the two agents are essentially the same. "I think off-label use [of armodafinil] is okay, because there are a lot of [safety] data for modafinil," Dr. Calabrese said in an interview.

Armodafinil (Nuvigil) has FDA approval for treating shift-work disorder, narcolepsy, and treated obstructed sleep apnea. He foresees no push for formal labeling of armodafinil for bipolar I depression because three phase III trials were run and only one was positive for efficacy. The two trials that failed to prove efficacy fell short not because of a blunted drug effect but because of an unexpectedly high response in the placebo group. This design flaw in two of the three pivotal trials likely doomed any hope of getting armodafinil labeled for this indication, he said.

"There is a role for armodafinil. It is something to try for patients" who need help in the things it affects, said Dr. Calabrese, professor of psychiatry and head of the mood disorders program at Case Western Reserve University in Cleveland. "It has stimulant-like properties that can improve concentration" and can help patients who are on another drug causing sedation, he added.

The study he ran enrolled patients who had cycled into a new major depressive episode after treatment with antimanic drugs for at least 4 weeks. Most patients were on antimanic monotherapy during the study, about 10% were on two antimanic drugs, and two patients were on three drugs. The researchers randomized 198 patients to receive 150 mg of armodafinil daily and 199 to placebo. An additional 32 patients initially received 200 mg armodafinil daily, but that arm was discontinued because of adverse effects.

After 8 weeks, the study’s primary endpoint – change in average, total clinician-rated, 30-item Inventory of Depressive Symptomatology (IDS) score – showed a 21.7 point drop with armodafinil and a 17.9 point drop with placebo, a statistically significant difference. The incidence of responder patients, those with at least a 50% reduction from their baseline IDS score, was 46% in the armodafinil arm and 34% in the placebo arm, a statistically significant difference and indicating a number needed to treat of nine to achieve one additional response over placebo.

The results also showed that the improvements in IDS score focused on five of the score’s 30 individual items: panic and phobic symptoms, appetite, concentration and decision making, energy and fatigability, and leaden paralysis and physical energy. In contrast, armodafinil had no apparent effect on core symptoms of depression. Armodafinil also produced no worsening of anxiety, sleep, or switch rates, and no meaningful trends toward gain or loss of weight.

The study was sponsored by Teva, which markets armodafinil (Nuvigil). Dr. Calabrese said that he has been a consultant to and received research support from Teva and more than a dozen other drug companies.

[email protected]

On Twitter @mitchelzoler

BARCELONA – Armodafinil, a drug with Food and Drug Administration approval to treat excessive sleepiness and narcolepsy, showed efficacy for improving concentration, energy, and appetite in a controlled study of nearly 400 patients with bipolar I depression.

"I think [armodafinil] is clinically useful because its efficacy appears complementary to the efficacy we see from other compounds," Dr. Joseph R. Calabrese said at the annual congress of the European College of Neuropsychopharmacology.

Mitchel L. Zoler/IMNG Medical Media

In addition to showing useful efficacy compared with placebo as adjunctive treatment, armodafinil also had a "very, very benign" adverse effect profile – its 6% dropout rate because of adverse effects was not statistically significant from the 4% rate in placebo patients.

Armodafinil is the R-enantiomer of modafinil, which means the two agents are essentially the same. "I think off-label use [of armodafinil] is okay, because there are a lot of [safety] data for modafinil," Dr. Calabrese said in an interview.

Armodafinil (Nuvigil) has FDA approval for treating shift-work disorder, narcolepsy, and treated obstructed sleep apnea. He foresees no push for formal labeling of armodafinil for bipolar I depression because three phase III trials were run and only one was positive for efficacy. The two trials that failed to prove efficacy fell short not because of a blunted drug effect but because of an unexpectedly high response in the placebo group. This design flaw in two of the three pivotal trials likely doomed any hope of getting armodafinil labeled for this indication, he said.

"There is a role for armodafinil. It is something to try for patients" who need help in the things it affects, said Dr. Calabrese, professor of psychiatry and head of the mood disorders program at Case Western Reserve University in Cleveland. "It has stimulant-like properties that can improve concentration" and can help patients who are on another drug causing sedation, he added.

The study he ran enrolled patients who had cycled into a new major depressive episode after treatment with antimanic drugs for at least 4 weeks. Most patients were on antimanic monotherapy during the study, about 10% were on two antimanic drugs, and two patients were on three drugs. The researchers randomized 198 patients to receive 150 mg of armodafinil daily and 199 to placebo. An additional 32 patients initially received 200 mg armodafinil daily, but that arm was discontinued because of adverse effects.

After 8 weeks, the study’s primary endpoint – change in average, total clinician-rated, 30-item Inventory of Depressive Symptomatology (IDS) score – showed a 21.7 point drop with armodafinil and a 17.9 point drop with placebo, a statistically significant difference. The incidence of responder patients, those with at least a 50% reduction from their baseline IDS score, was 46% in the armodafinil arm and 34% in the placebo arm, a statistically significant difference and indicating a number needed to treat of nine to achieve one additional response over placebo.

The results also showed that the improvements in IDS score focused on five of the score’s 30 individual items: panic and phobic symptoms, appetite, concentration and decision making, energy and fatigability, and leaden paralysis and physical energy. In contrast, armodafinil had no apparent effect on core symptoms of depression. Armodafinil also produced no worsening of anxiety, sleep, or switch rates, and no meaningful trends toward gain or loss of weight.

The study was sponsored by Teva, which markets armodafinil (Nuvigil). Dr. Calabrese said that he has been a consultant to and received research support from Teva and more than a dozen other drug companies.

[email protected]

On Twitter @mitchelzoler

BARCELONA – Lurasidone, an atypical antipsychotic approved by the Food and Drug Administration last June for the treatment of depression in patients with bipolar I disorder, has the potential to become a first-line treatment for these patients as physicians grow more familiar and comfortable with the drug, Dr. Joseph R. Calabrese said at the annual Congress of the European College of Neuropsychopharmacology.

In addition to showing significant efficacy for reducing depression in bipolar I patients when used as either monotherapy or as adjunctive therapy in a pair of phase III trials, lurasidone (Latuda) "does not have the metabolic burden caused by some other drugs" used in these patients, and also showed no statistically significant increase in dropout rates compared with placebo. The discontinuation rate because of adverse effects was especially low when the drug was administered at a dosage of 20-60 mg/day. This safety finding is "remarkable," said Dr. Calabrese, professor of psychiatry and head of the mood disorders program at Case Western Reserve University in Cleveland.

Mitchel L. Zoler/IMNG Medical Media

The results from the two phase III trials provide "unequivocal evidence that the drug has short-term efficacy for patients with depressive episodes in bipolar I disorder. I think the evidence is very persuasive," Dr. Calabrese said in an interview. "I think this drug will be used adjunctively at first, but with more familiarity, physicians will start using it up front. The No. 1 attraction for first-line therapy is no metabolic burden; that’s a huge issue. And sedation is minimal." Dr. Calabrese stressed that the trial results showed no dropouts because of sedation, and 10%-15% of patients reported a sedation effect, compared with the 40% rate typically seen with lamotrigine (Lamictal).

One of the trials assessed lurasidone as an adjunctive treatment in 340 patients already on treatment with lithium or valproate. After 6 weeks, patients on lurasidone plus one of the other drugs had an average drop from baseline in their Montgomery-Åsberg Depression Rating Scale (MADRS) score of 17.1 points, compared with an average 13.5-point drop in the control patients who were on lithium or valproate plus placebo, a statistically significant difference. Fifty-seven percent of the 179 patients receiving lurasidone had at least a 50% drop in their MADRS score, compared with 42% of 161 patients in the control arm. Remission – achievement of a MADRS score of 12 or less – occurred in half the lurasidone patients and 35% of the controls.

Also notable was the impact the drug had on the 10 individual components of the MADRS score. Six of these 10 items showed statistically significant reductions with lurasidone treatment, including the two core measures of depression, apparent sadness and reported sadness.

The second trial tested lurasidone as monotherapy, at two different dosages, either 20-60 mg/day or 80-120 mg/day, and both were compared with placebo during 6 weeks of treatment, with a total of 485 patients randomized and completing 6 weeks on treatment. Lurasidone resulted in a similar pattern of efficacy, with 42% (lower dosage) and 40% of patients having their MADRS score drop to 12 points or less, compared with a 25% remission rate in the placebo group. Both dosages of lurasidone led to statistically significant reductions in 7 of the 10 MADRS component measures compared with the control arm.

The monotherapy study also showed that while the lower lurasidone dosage was just as effective as the higher dosage, it was more tolerable, with lower rates of akathisia and extrapyramidal symptoms. Lurasidone appears to produce low rates of sedation, appetite stimulation, and weight gain because of its negligible binding to the histamine₁ receptor, Dr. Calabrese said. In the adjunctive study, lurasidone treatment resulted in virtually no change in weight or body mass index, and very small changes in cholesterol, triglycerides, and fasting glucose.

The two trials were sponsored by Sunovion, the company that markets lurasidone. Dr. Calabrese said he has been a consultant to and has received research support from Sunovion as well as from more than a dozen other drug companies.

[email protected]

On Twitter @mitchelzoler

BARCELONA – Lurasidone, an atypical antipsychotic approved by the Food and Drug Administration last June for the treatment of depression in patients with bipolar I disorder, has the potential to become a first-line treatment for these patients as physicians grow more familiar and comfortable with the drug, Dr. Joseph R. Calabrese said at the annual Congress of the European College of Neuropsychopharmacology.

In addition to showing significant efficacy for reducing depression in bipolar I patients when used as either monotherapy or as adjunctive therapy in a pair of phase III trials, lurasidone (Latuda) "does not have the metabolic burden caused by some other drugs" used in these patients, and also showed no statistically significant increase in dropout rates compared with placebo. The discontinuation rate because of adverse effects was especially low when the drug was administered at a dosage of 20-60 mg/day. This safety finding is "remarkable," said Dr. Calabrese, professor of psychiatry and head of the mood disorders program at Case Western Reserve University in Cleveland.

Mitchel L. Zoler/IMNG Medical Media

The results from the two phase III trials provide "unequivocal evidence that the drug has short-term efficacy for patients with depressive episodes in bipolar I disorder. I think the evidence is very persuasive," Dr. Calabrese said in an interview. "I think this drug will be used adjunctively at first, but with more familiarity, physicians will start using it up front. The No. 1 attraction for first-line therapy is no metabolic burden; that’s a huge issue. And sedation is minimal." Dr. Calabrese stressed that the trial results showed no dropouts because of sedation, and 10%-15% of patients reported a sedation effect, compared with the 40% rate typically seen with lamotrigine (Lamictal).

One of the trials assessed lurasidone as an adjunctive treatment in 340 patients already on treatment with lithium or valproate. After 6 weeks, patients on lurasidone plus one of the other drugs had an average drop from baseline in their Montgomery-Åsberg Depression Rating Scale (MADRS) score of 17.1 points, compared with an average 13.5-point drop in the control patients who were on lithium or valproate plus placebo, a statistically significant difference. Fifty-seven percent of the 179 patients receiving lurasidone had at least a 50% drop in their MADRS score, compared with 42% of 161 patients in the control arm. Remission – achievement of a MADRS score of 12 or less – occurred in half the lurasidone patients and 35% of the controls.

Also notable was the impact the drug had on the 10 individual components of the MADRS score. Six of these 10 items showed statistically significant reductions with lurasidone treatment, including the two core measures of depression, apparent sadness and reported sadness.

The second trial tested lurasidone as monotherapy, at two different dosages, either 20-60 mg/day or 80-120 mg/day, and both were compared with placebo during 6 weeks of treatment, with a total of 485 patients randomized and completing 6 weeks on treatment. Lurasidone resulted in a similar pattern of efficacy, with 42% (lower dosage) and 40% of patients having their MADRS score drop to 12 points or less, compared with a 25% remission rate in the placebo group. Both dosages of lurasidone led to statistically significant reductions in 7 of the 10 MADRS component measures compared with the control arm.

The monotherapy study also showed that while the lower lurasidone dosage was just as effective as the higher dosage, it was more tolerable, with lower rates of akathisia and extrapyramidal symptoms. Lurasidone appears to produce low rates of sedation, appetite stimulation, and weight gain because of its negligible binding to the histamine₁ receptor, Dr. Calabrese said. In the adjunctive study, lurasidone treatment resulted in virtually no change in weight or body mass index, and very small changes in cholesterol, triglycerides, and fasting glucose.

The two trials were sponsored by Sunovion, the company that markets lurasidone. Dr. Calabrese said he has been a consultant to and has received research support from Sunovion as well as from more than a dozen other drug companies.

[email protected]

On Twitter @mitchelzoler

BARCELONA – Lurasidone, an atypical antipsychotic approved by the Food and Drug Administration last June for the treatment of depression in patients with bipolar I disorder, has the potential to become a first-line treatment for these patients as physicians grow more familiar and comfortable with the drug, Dr. Joseph R. Calabrese said at the annual Congress of the European College of Neuropsychopharmacology.

In addition to showing significant efficacy for reducing depression in bipolar I patients when used as either monotherapy or as adjunctive therapy in a pair of phase III trials, lurasidone (Latuda) "does not have the metabolic burden caused by some other drugs" used in these patients, and also showed no statistically significant increase in dropout rates compared with placebo. The discontinuation rate because of adverse effects was especially low when the drug was administered at a dosage of 20-60 mg/day. This safety finding is "remarkable," said Dr. Calabrese, professor of psychiatry and head of the mood disorders program at Case Western Reserve University in Cleveland.

Mitchel L. Zoler/IMNG Medical Media

The results from the two phase III trials provide "unequivocal evidence that the drug has short-term efficacy for patients with depressive episodes in bipolar I disorder. I think the evidence is very persuasive," Dr. Calabrese said in an interview. "I think this drug will be used adjunctively at first, but with more familiarity, physicians will start using it up front. The No. 1 attraction for first-line therapy is no metabolic burden; that’s a huge issue. And sedation is minimal." Dr. Calabrese stressed that the trial results showed no dropouts because of sedation, and 10%-15% of patients reported a sedation effect, compared with the 40% rate typically seen with lamotrigine (Lamictal).

One of the trials assessed lurasidone as an adjunctive treatment in 340 patients already on treatment with lithium or valproate. After 6 weeks, patients on lurasidone plus one of the other drugs had an average drop from baseline in their Montgomery-Åsberg Depression Rating Scale (MADRS) score of 17.1 points, compared with an average 13.5-point drop in the control patients who were on lithium or valproate plus placebo, a statistically significant difference. Fifty-seven percent of the 179 patients receiving lurasidone had at least a 50% drop in their MADRS score, compared with 42% of 161 patients in the control arm. Remission – achievement of a MADRS score of 12 or less – occurred in half the lurasidone patients and 35% of the controls.

Also notable was the impact the drug had on the 10 individual components of the MADRS score. Six of these 10 items showed statistically significant reductions with lurasidone treatment, including the two core measures of depression, apparent sadness and reported sadness.

The second trial tested lurasidone as monotherapy, at two different dosages, either 20-60 mg/day or 80-120 mg/day, and both were compared with placebo during 6 weeks of treatment, with a total of 485 patients randomized and completing 6 weeks on treatment. Lurasidone resulted in a similar pattern of efficacy, with 42% (lower dosage) and 40% of patients having their MADRS score drop to 12 points or less, compared with a 25% remission rate in the placebo group. Both dosages of lurasidone led to statistically significant reductions in 7 of the 10 MADRS component measures compared with the control arm.

The monotherapy study also showed that while the lower lurasidone dosage was just as effective as the higher dosage, it was more tolerable, with lower rates of akathisia and extrapyramidal symptoms. Lurasidone appears to produce low rates of sedation, appetite stimulation, and weight gain because of its negligible binding to the histamine₁ receptor, Dr. Calabrese said. In the adjunctive study, lurasidone treatment resulted in virtually no change in weight or body mass index, and very small changes in cholesterol, triglycerides, and fasting glucose.

The two trials were sponsored by Sunovion, the company that markets lurasidone. Dr. Calabrese said he has been a consultant to and has received research support from Sunovion as well as from more than a dozen other drug companies.

[email protected]

On Twitter @mitchelzoler

The therapeutic consequences can be depressing!

A study published recently found a difference in brain blood flow between unipolar depression, also known as major depressive disorder (MDD), and the depressive phase of bipolar I (BD I) and bipolar II (BD II) disorders, known as bipolar depression.¹ Researchers performed arterial spin labeling and submitted the resulting data to pattern recognition analysis to correctly classify 81% of subjects. This type of investigation augurs that objective biomarkers might halt the unrelenting misdiagnosis of bipolar depression as MDD and end the iatrogenic suffering of millions of bipolar disorder patients who became victims of a “therapeutic misadventure.”

It is perplexing that this problem has festered so long, simply because the two types of depression look deceptively alike.

This takes me back to my days in residency

Although I trained in one of the top psychiatry programs at the time, I was never taught that I must first classify my depressed patient as unipolar or bipolar before embarking on a treatment plan. Back then, “depression was depression” and treatment was the same for all depressed patients: Start with a tricyclic antidepressant (TCA). If there is no response within a few weeks, consider a different TCA or move to a monoamine oxidase inhibitor. If that does not work, perform electroconvulsive therapy (ECT).

Quite a few depressed patients actually worsened on antidepressant drugs, becoming agitated, irritable, and angry—yet clinicians did not recognize that change as a switch to irritable mania or hypomania, or a mixed depressed state. In fact, in those days, patients suffering mania or hypomania were expected to be euphoric and expansive, and the fact that almost one-half of bipolar mania presents with irritable, rather than euphoric, mood was not widely recognized, either.

I recall psychodynamic discussions as a resident about the anger and hostility that some patients with depression manifest. It was not widely recognized that treating bipolar depression with an antidepressant might lead to any of four undesirable switches: mania, hypomania, mixed state, or rapid cycling. We saw patients with all of these complications and simply labeled their condition “treatment-resistant depression,” especially if the patient switched to rapid cycling with recurrent depressions (which often happens with BD II patients who receive antidepressant monotherapy).

Frankly, BD II was not on our radar screen, and practically all such patients were given a misdiagnosis of MDD. No wonder we all marveled at how ECT finally helped out the so-called treatment-resistant patients!

Sadly, the state of the art treatment of bipolar depression back then was actually a state of incomplete knowledge. Okay—call it a state of ignorance wrapped in good intentions.

The dots did not get connected…

There were phenomenologic clues that, had we noticed them, could have corrected our clinical blind spot about the ways bipolar depression is different from unipolar depression. Yet we did not connect the dots about how bipolar depression is different from MDD (Table).

Treatment clues also should have opened our eyes to the different types of depression:

Clue #1: Patients with treatment-resistant depression often responded when lithium was added to an antidepressant. This led to the belief that lithium has antidepressant properties, instead of clueing us that treatment-resistant depression is actually a bipolar type of depression.

Clue #2: Likewise, patients with treatment-resistant depression improved when an antipsychotic agent, which is also anti-manic, was added to an antidepressant (seasoned clinicians might remember the amitriptyline-perphenazine combination pill, sold as Triavil, that was a precursor of the olanzapine-fluoxetine combination developed a few years ago to treat bipolar depression).

Clue #3: ECT exerted efficacy in patients who failed an antidepressant or who got worse taking one (ie, switched to a mixed state).

A new age of therapeutics

In the past few years, we’ve witnessed the development of several pharmacotherapeutic agents for bipolar depression. First, the olanzapine-fluoxetine combination was approved for this indication in 2003. That was followed by quetiapine monotherapy in 2005 and, most recently, in 2013, lurasidone  (both as monotherapy and as an adjunct to a mood stabilizer).

With those three FDA-approved options for bipolar depression, clinicians can now treat this type of depression without putting the patient at risk of complications that ensue when anti­depressants approved only for MDD are used erroneously as monotherapy for bipolar depression.

These days, psychiatry residents are rigorously trained to differentiate unipolar and bipolar depression and to select the most appropriate, evidence-based treatment for bipolar depression. The state of ignorance surrounding this psychiatric condition is lifting, although there are pockets of persisting nonrecognition in some settings. Gaps in knowledge underpin and perpetuate hoary practices, but innovative research—such as the study cited here on brain blood-flow biomarkers—is the ultimate antidote to ignorance.

The therapeutic consequences can be depressing!

A study published recently found a difference in brain blood flow between unipolar depression, also known as major depressive disorder (MDD), and the depressive phase of bipolar I (BD I) and bipolar II (BD II) disorders, known as bipolar depression.¹ Researchers performed arterial spin labeling and submitted the resulting data to pattern recognition analysis to correctly classify 81% of subjects. This type of investigation augurs that objective biomarkers might halt the unrelenting misdiagnosis of bipolar depression as MDD and end the iatrogenic suffering of millions of bipolar disorder patients who became victims of a “therapeutic misadventure.”

It is perplexing that this problem has festered so long, simply because the two types of depression look deceptively alike.

This takes me back to my days in residency

Although I trained in one of the top psychiatry programs at the time, I was never taught that I must first classify my depressed patient as unipolar or bipolar before embarking on a treatment plan. Back then, “depression was depression” and treatment was the same for all depressed patients: Start with a tricyclic antidepressant (TCA). If there is no response within a few weeks, consider a different TCA or move to a monoamine oxidase inhibitor. If that does not work, perform electroconvulsive therapy (ECT).

Quite a few depressed patients actually worsened on antidepressant drugs, becoming agitated, irritable, and angry—yet clinicians did not recognize that change as a switch to irritable mania or hypomania, or a mixed depressed state. In fact, in those days, patients suffering mania or hypomania were expected to be euphoric and expansive, and the fact that almost one-half of bipolar mania presents with irritable, rather than euphoric, mood was not widely recognized, either.

I recall psychodynamic discussions as a resident about the anger and hostility that some patients with depression manifest. It was not widely recognized that treating bipolar depression with an antidepressant might lead to any of four undesirable switches: mania, hypomania, mixed state, or rapid cycling. We saw patients with all of these complications and simply labeled their condition “treatment-resistant depression,” especially if the patient switched to rapid cycling with recurrent depressions (which often happens with BD II patients who receive antidepressant monotherapy).

Frankly, BD II was not on our radar screen, and practically all such patients were given a misdiagnosis of MDD. No wonder we all marveled at how ECT finally helped out the so-called treatment-resistant patients!

Sadly, the state of the art treatment of bipolar depression back then was actually a state of incomplete knowledge. Okay—call it a state of ignorance wrapped in good intentions.

The dots did not get connected…

There were phenomenologic clues that, had we noticed them, could have corrected our clinical blind spot about the ways bipolar depression is different from unipolar depression. Yet we did not connect the dots about how bipolar depression is different from MDD (Table).

Treatment clues also should have opened our eyes to the different types of depression:

Clue #1: Patients with treatment-resistant depression often responded when lithium was added to an antidepressant. This led to the belief that lithium has antidepressant properties, instead of clueing us that treatment-resistant depression is actually a bipolar type of depression.

Clue #2: Likewise, patients with treatment-resistant depression improved when an antipsychotic agent, which is also anti-manic, was added to an antidepressant (seasoned clinicians might remember the amitriptyline-perphenazine combination pill, sold as Triavil, that was a precursor of the olanzapine-fluoxetine combination developed a few years ago to treat bipolar depression).

Clue #3: ECT exerted efficacy in patients who failed an antidepressant or who got worse taking one (ie, switched to a mixed state).

A new age of therapeutics

In the past few years, we’ve witnessed the development of several pharmacotherapeutic agents for bipolar depression. First, the olanzapine-fluoxetine combination was approved for this indication in 2003. That was followed by quetiapine monotherapy in 2005 and, most recently, in 2013, lurasidone  (both as monotherapy and as an adjunct to a mood stabilizer).

With those three FDA-approved options for bipolar depression, clinicians can now treat this type of depression without putting the patient at risk of complications that ensue when anti­depressants approved only for MDD are used erroneously as monotherapy for bipolar depression.

These days, psychiatry residents are rigorously trained to differentiate unipolar and bipolar depression and to select the most appropriate, evidence-based treatment for bipolar depression. The state of ignorance surrounding this psychiatric condition is lifting, although there are pockets of persisting nonrecognition in some settings. Gaps in knowledge underpin and perpetuate hoary practices, but innovative research—such as the study cited here on brain blood-flow biomarkers—is the ultimate antidote to ignorance.

The therapeutic consequences can be depressing!

A study published recently found a difference in brain blood flow between unipolar depression, also known as major depressive disorder (MDD), and the depressive phase of bipolar I (BD I) and bipolar II (BD II) disorders, known as bipolar depression.¹ Researchers performed arterial spin labeling and submitted the resulting data to pattern recognition analysis to correctly classify 81% of subjects. This type of investigation augurs that objective biomarkers might halt the unrelenting misdiagnosis of bipolar depression as MDD and end the iatrogenic suffering of millions of bipolar disorder patients who became victims of a “therapeutic misadventure.”

It is perplexing that this problem has festered so long, simply because the two types of depression look deceptively alike.

This takes me back to my days in residency

Although I trained in one of the top psychiatry programs at the time, I was never taught that I must first classify my depressed patient as unipolar or bipolar before embarking on a treatment plan. Back then, “depression was depression” and treatment was the same for all depressed patients: Start with a tricyclic antidepressant (TCA). If there is no response within a few weeks, consider a different TCA or move to a monoamine oxidase inhibitor. If that does not work, perform electroconvulsive therapy (ECT).

Quite a few depressed patients actually worsened on antidepressant drugs, becoming agitated, irritable, and angry—yet clinicians did not recognize that change as a switch to irritable mania or hypomania, or a mixed depressed state. In fact, in those days, patients suffering mania or hypomania were expected to be euphoric and expansive, and the fact that almost one-half of bipolar mania presents with irritable, rather than euphoric, mood was not widely recognized, either.

I recall psychodynamic discussions as a resident about the anger and hostility that some patients with depression manifest. It was not widely recognized that treating bipolar depression with an antidepressant might lead to any of four undesirable switches: mania, hypomania, mixed state, or rapid cycling. We saw patients with all of these complications and simply labeled their condition “treatment-resistant depression,” especially if the patient switched to rapid cycling with recurrent depressions (which often happens with BD II patients who receive antidepressant monotherapy).

Frankly, BD II was not on our radar screen, and practically all such patients were given a misdiagnosis of MDD. No wonder we all marveled at how ECT finally helped out the so-called treatment-resistant patients!

Sadly, the state of the art treatment of bipolar depression back then was actually a state of incomplete knowledge. Okay—call it a state of ignorance wrapped in good intentions.

The dots did not get connected…

There were phenomenologic clues that, had we noticed them, could have corrected our clinical blind spot about the ways bipolar depression is different from unipolar depression. Yet we did not connect the dots about how bipolar depression is different from MDD (Table).

Treatment clues also should have opened our eyes to the different types of depression:

Clue #1: Patients with treatment-resistant depression often responded when lithium was added to an antidepressant. This led to the belief that lithium has antidepressant properties, instead of clueing us that treatment-resistant depression is actually a bipolar type of depression.

Clue #2: Likewise, patients with treatment-resistant depression improved when an antipsychotic agent, which is also anti-manic, was added to an antidepressant (seasoned clinicians might remember the amitriptyline-perphenazine combination pill, sold as Triavil, that was a precursor of the olanzapine-fluoxetine combination developed a few years ago to treat bipolar depression).

Clue #3: ECT exerted efficacy in patients who failed an antidepressant or who got worse taking one (ie, switched to a mixed state).

A new age of therapeutics

In the past few years, we’ve witnessed the development of several pharmacotherapeutic agents for bipolar depression. First, the olanzapine-fluoxetine combination was approved for this indication in 2003. That was followed by quetiapine monotherapy in 2005 and, most recently, in 2013, lurasidone  (both as monotherapy and as an adjunct to a mood stabilizer).

With those three FDA-approved options for bipolar depression, clinicians can now treat this type of depression without putting the patient at risk of complications that ensue when anti­depressants approved only for MDD are used erroneously as monotherapy for bipolar depression.

These days, psychiatry residents are rigorously trained to differentiate unipolar and bipolar depression and to select the most appropriate, evidence-based treatment for bipolar depression. The state of ignorance surrounding this psychiatric condition is lifting, although there are pockets of persisting nonrecognition in some settings. Gaps in knowledge underpin and perpetuate hoary practices, but innovative research—such as the study cited here on brain blood-flow biomarkers—is the ultimate antidote to ignorance.